Title

Author

Term of Award

Degree Name

Document Type and Release Option

Thesis (restricted to Georgia Southern)

Department

Department of Biology

Committee Chair

Karin Scarpinato

Committee Member 1

Johanne Lewis

Committee Member 2

Marina Eremeeva

Abstract

Mismatch repair (MMR) proteins have previously been implicated to play a role in cellular apoptotic response to chemotherapeutics. However, what has not been established is how these proteins participate in both repair events and apoptosis. We are here investigating if cellular compartmentalization of disparate MMR functions plays a role in orchestrating these two opposite responses to DNA damage. Initial data from our lab and others indicated that MMR proteins can participate in apoptosis via a repair-dependent and -independent mechanism, dependent on the type of damage. Nuclear influx of MSH2 may be part of the repair-independent mechanism. Results from confocal microscopy and fluorescent linked immunosorbent assays showed both a corollary movement of MSH2 with the MMR repair protein EXO1, as well as an ability of the two proteins to bind with one another. Caspase-3 assay’s conducted on cells treated with either the intrastrand crosslink drug Cisplatin or the frameshift mutation drug ICR191 showed that only cells with normal expression of MSH2 and EXO1 as well as those cells treated with Cisplatin showed a significant apoptotic response above the control. These data suggest that EXO1 plays a role in MSH2’s movement into the nucleus when treated with a drug that induces apoptosis, and that the switch between repair and repair-independent apoptotic response may be aided by cellular compartmentalization.